The long term objective of this fellowship is to provide me with a thorough knowledge of the effects of mitochondria on intracellular Ca2+ signaling and the expertise in mathematical modeling necessary to establish an independent research program that combines experiment and modeling. In the future I am interested in conducting cell biological and biophysical research on the effects of mitochondrial disorders on the nervous system. Aberrant Ca2+ signaling, and especially the opening of the mitochondrial transition pore by Ca2+, free radicals and other modulators, has been implicated in neuronal and other cell death in pathological situations. The specific research aims of this fellowship are 1) to extend Dr. Keizer s efforts to build mitochondria into Ca2+ signaling models by incorporating the mitochondrial transition pore and 2) to solve these systems in two and three spatial dimensions. The goal is to be able to make testable predictions about the effect of mitochondrial function on both normal Ca2+ signaling and pathological processes involving Ca2+ and mitochondria in cells.